Tularemia: Epidemiology, Ecology, Genomics, Immunity and Pathogenesis

Tularemia is a severe anthropozoonosis caused by Francisella tularensis. The genus Francisella contains five species: F. tularensis, F. philomiragia, F. hispaniensis, F. noatunensis and F. novicida. First described in 1911 in Tulare County, California, it has since been reported worldwide, capable of infecting more than 250 vertebrates and invertebrate species. Although it causes disease in various animal species, no animal has been identified as a main reservoir of this pathogen. Humans acquire infection by several routes, including direct contact with infected animals, ingestion of water or food contaminated by infected animals, exposure to infected arthropod vectors or by inhalation of infective aerosols resulting in pneumonic, oropharyngeal, glandular, ulceroglandular or oculoglandular tularemia. The clinical presentation of human tularemia depends on route of the infection, the causative Francisella strain, and the immune response of the host. A live attenuated vaccine (LVS) has been available for more than 50 years, however, unlikely to become licensed in the future due to a lack of understanding of the genetic basis for its attenuation. Due to the ease of its dissemination, its multiple routes of infection, its low dose of infection, severe morbidity, and high rate of mortality, F. tularensis subsp. tularensis has been classified as a category A bioterrorism agent by the CDC. Many virulence factors of F. tularensis have been discovered and investigated, but more in-depth host pathogen interaction analyses are needed to define mechanisms of pathogenicity and virulence of this unique pathogen.